Inhalant Formulation Containing Sulfoalkyl Ether Cyclodextrin and Corticosteroid

1 . An aqueous liquid formulation comprising a therapeutically effective amount of corticosteroid dissolved therein, SAE-CD, and an aqueous liquid carrier, wherein the molar ratio of SAE-CD to corticosteroid is greater than 10:1.

2 . The formulation of claim 1 , wherein the corticosteroid is selected from the group consisting of beclomethasone, beclomethasone dipropionate, beclomethasone monopropionate, budesonide, ciclesonide, desisobutyryl-ciclesonide, flunisolide, fluticasone, fluticasone propionate, mometasone, mometasone furoate, icomethasone enbutate, tixocortol 21-pivalate, and triamcinolone acetonide

3 . The formulation of claim 1 , wherein the molar ratio of SAE-CD to corticosteroid is greater than about 10:1 to about 10,000:1.

4 . The formulation of claim 1 , wherein the formulation is a substantially clear solution comprising less than 5% wt. undissolved corticosteroid.

5 . The formulation of claim 1 , comprising 21.5±2% wt./wt. or less of SAE-CD.

6 . The formulation of claim 1 , wherein the SAE-CD is present at a concentration of about 10 mg to about 500 mg of SAE-CD per ml of formulation.

7 . The formulation of claim 1 , wherein the formulation has a shelf-life of at least 6 months.

8 . The formulation of claim 1 further comprising one or more therapeutic agents independently selected at each occurrence from the group consisting of a β2-adrenoreceptor agonist, a dopamine (D2) receptor agonist, a topical anesthetic, an anticholinergic agent, IL-5 inhibitor, antisense modulator of IL-5, milrinone (1,6-dihydro-2-methyl-6-oxo-[3,4′-bipyridine]-5-carbonitrile), milrinone lactate, tryptase inhibitor, tachykinin receptor antagonist, leukotriene receptor antagonist, 5-lypoxygenase inhibitor, and anti-IgE antibody.

9 . The formulation of claim 8 , wherein the corticosteroid is present in a molar excess over the other therapeutic agent.

10 . The formulation of claim 8 , wherein the other therapeutic agent is present in a molar excess over the corticosteroid.

11 . The formulation of claim 8 , wherein the SAE-CD is present in a molar excess over the other therapeutic agent.

12 . The formulation of claim 1 , wherein the SAE-CD is a compound of the Formula 1:

wherein:

n is 4, 5 or 6;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are each, independently, —O— or a —O—(C 2 -C 6 alkylene)-SO 3 − group, wherein at least one of R 1 - 9 is independently a —O—(C 2 -C 6 alkylene)-SO 3 − group, a —O—(CH 2 ) m SO 3 − group wherein m is 2 to 6, —OCH 2 CH 2 CH 2 SO 3 − , or —OCH 2 CH 2 CH 2 CH 2 SO 3 − ); and

S 1 , S 2 , S 3 , S 4 , S 5 , S 6 , S 7 , S 8 and S 9 are each, independently, a pharmaceutically acceptable cation.

13 . The formulation of claim 12 , wherein the SAE-CD is selected from the group consisting of:

SAEx-α-CD

SAEy-β-CD

SAEz-γ-CD

SEEx-α-CD

SEEy-β-CD

SEEz-γ-CD

SPEx-α-CD

SPEy-β-CD

SPEz-γ-CD

SBEx-α-CD

SBEy-β-CD

SBEz-γ-CD

SPtEx-α-CD

SPtEy-β-CD

SPtEz-γ-CD

SHEx-α-CD

SHEy-β-CD

SHEz-γ-CD.

14 . A solid composition prepared by drying a formulation according to claim 1 .

15 . A liquid formulation according to claim 1 , wherein the formulation is adapted for nasal, oral, ophthalmic, otic, or topical administration.

16 . A method of treating a disease or disorder of the airways, in a subject in need thereof, comprising administering via inhalation the formulation of claim 1 , the corticosteroid being present in an amount sufficient to provide a mean plasma AUCt of 160-1600 pg*h/ml.

17 . A method of providing in a subject:

(a) a mean plasma AUCt of 150-1600 pg*h/ml for the corticosteroid in an individual subject comprising: administering to the subject, via nebulization, 48-220 μg, as dose to subject, of a corticosteroid dissolved in an aqueous liquid carrier comprising sulfoalkyl ether cyclodextrin; or

(b) a mean plasma AUCt, normalized for dose of corticosteroid to subject, of at least 6 (pg*h/ml)/μg of corticosteroid delivered, as dose to subject, comprising: administering to the subject, via nebulization, at least 45 μg of corticosteroid dissolved in an aqueous liquid carrier comprising sulfoalkyl ether cyclodextrin; or

(c) a mean AUCi, normalized for dose of corticosteroid to subject, of at least 8 (pg*h/ml)/μg of corticosteroid delivered, as dose to subject, comprising: administering to the subject, via nebulization, at least 45 μg of corticosteroid dissolved in an aqueous liquid carrier comprising sulfoalkyl ether cyclodextrin.

18 . A method of reducing the amount of time required to provide a therapeutically effective amount of corticosteroid to a subject by inhalation of a corticosteroid-containing composition with a nebulizer, the method comprising the steps of: including SAE-CD in the composition in an amount sufficient to solubilize the corticosteroid to form an inhalable aqueous corticosteroid-containing solution; and

administering the solution to the subject by inhalation with a nebulizer, wherein the amount of time required to provide a therapeutically effective amount of corticosteroid to the subject with the solution is reduced as compared to the amount of time required to provide a therapeutically effective amount of corticosteroid to the subject with a corticosteroid-containing suspension comprising the same amount or concentration of corticosteroid when the suspension and solution are administered under otherwise similar nebulization conditions.